Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia

Objectives Diazoxide (DZX) is the drug of choice for treating hyperinsulinaemic hypoglycaemia (HH), and it has potentially serious adverse effects. We studied the safety and efficacy of low-dose DZX in small-for-gestational-age (SGA) infants with HH. Design An observational cohort study from 1 September 2014 to 31 September 2020. Setting A tertiary Women's and Children's Hospital in Singapore. Patients All SGA infants with HH. Intervention Diazoxide, at 3-5 mg/kg/day. Main outcome measures Short-term outcomes; adverse drug events and fasting studies to determine 'safe to go home' and 'resolution' of HH. Results Among 71 836 live births, 11 493 (16%) were SGA. Fifty-six (0.5%) SGA infants with HH were identified, of which 27 (47%) with a mean gestational age of 36.4 +/- 2 weeks and birth weight of 1942 +/- 356 g required DZX treatment. Diazoxide was initiated at 3 mg/kg/day at a median age of 10 days. The mean effective dose was 4.6 +/- 2.2 mg/kg/day, with 24/27 (89%) receiving 3-5 mg/kg/day. Generalised hypertrichosis occurred in 2 (7.4%) and fluid retention in 1 (3.7%) infant. A fasting study was performed before home while on DZX in 26/27 (96%) cases. Diazoxide was discontinued at a median age of 63 days (9-198 days), and resolution of HH was confirmed in 26/27 (96%) infants on passing a fasting study. Conclusion Our study demonstrates that low-dose DZX effectively treats SGA infants with HH as measured by fasting studies. Although the safety profile was excellent, minimal adverse events were still observed with DZX, even at low doses. SGA infants are at risk of hyperinsulinaemic hypoglycaemia and neuronal injury. We report that low dose diazoxide (3-5 mg/kg/day) effectively treats hyperinsulinaemic hypoglycaemia in these SGA infants. Its safety profile was excellent, but adverse events were still observed.

Automated summary

This study showed that low-dose diazoxide effectively treats hyperinsulinaemic hypoglycaemia in SGA infants as measured by fasting studies. The safety profile was excellent, but there were still minimal adverse events observed.